Cardiovascular problems represent the major cause of death and disability in the developed world. Atherosclerosis is associated with the development of many cardiovascular disorders. Atherosclerosis is characterized by the deposits or plaques of lipids and other blood derivatives in the arterial walls of, e.g., aorta, coronary arteries and carotid. Atherosclerotic plaques begin as fatty streaks underlying the endothelium of large arteries. Recruitment of macrophages and their subsequent uptake of LDL derived cholesterol are the major cellular events contributing to fatty streak formation. These plaques can be calcified to a greater or lesser extent according to the progression of the process. They are also associated with the accumulation of fatty deposits consisting mainly of cholesterol esters in the arteries. Cholesterol accumulates in the foam cells of the arterial wall, thereby narrowing the lumen and decreasing the flow of blood. This is accompanied by a thickening of the arterial wall, with hypertrophy of the smooth muscle, the appearance of foam cells and the accumulation of the fibrous tissue. Hypercholesterolemia can therefore result in very serious cardiovascular pathologies such as infarction, peripheral vascular disease, stroke, sudden death, cardiac decompensation, cerebral vascular accidents and the like.
There is a recognized need in the art for better and more reliable means for treating and preventing atherosclerosis and medical conditions that are associated with or mediated by atherosclerosis. The present invention is directed to this and other needs.